NOVA1_MOUSE
ID NOVA1_MOUSE Reviewed; 507 AA.
AC Q9JKN6; Q8C8B9;
DT 04-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=RNA-binding protein Nova-1 {ECO:0000305};
DE AltName: Full=Neuro-oncological ventral antigen 1;
DE AltName: Full=Ventral neuron-specific protein 1;
GN Name=Nova1 {ECO:0000312|MGI:MGI:104297};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 15-507.
RC STRAIN=CBA/J; TISSUE=Brain;
RX PubMed=11003693; DOI=10.1007/s003350010167;
RA Ward-Bailey P.F., Wood B., Johnson K.R., Bronson R.T., Donahue L.R.,
RA Davisson M.T.;
RT "Neuromuscular ataxia: a new spontaneous mutation in the mouse.";
RL Mamm. Genome 11:820-823(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 264-507.
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, RNA-BINDING, AND
RP MUTAGENESIS OF LEU-444.
RX PubMed=8558240; DOI=10.1523/jneurosci.16-03-01114.1996;
RA Buckanovich R.J., Yang Y.Y., Darnell R.B.;
RT "The onconeural antigen Nova-1 is a neuron-specific RNA-binding protein,
RT the activity of which is inhibited by paraneoplastic antibodies.";
RL J. Neurosci. 16:1114-1122(1996).
RN [5]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=9154818; DOI=10.1128/mcb.17.6.3194;
RA Buckanovich R.J., Darnell R.B.;
RT "The neuronal RNA binding protein Nova-1 recognizes specific RNA targets in
RT vitro and in vivo.";
RL Mol. Cell. Biol. 17:3194-3201(1997).
RN [6]
RP FUNCTION, AND INVOLVEMENT IN NEURONAL DISEASE.
RX PubMed=10719891; DOI=10.1016/s0896-6273(00)80900-9;
RA Jensen K.B., Dredge B.K., Stefani G., Zhong R., Buckanovich R.J.,
RA Okano H.J., Yang Y.Y.-L., Darnell R.B.;
RT "Nova-1 regulates neuron-specific alternative splicing and is essential for
RT neuronal viability.";
RL Neuron 25:359-371(2000).
RN [7]
RP INTERACTION WITH PTBP2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10829067; DOI=10.1073/pnas.110128397;
RA Polydorides A.D., Okano H.J., Yang Y.Y.L., Stefani G., Darnell R.B.;
RT "A brain-enriched polypyrimidine tract-binding protein antagonizes the
RT ability of Nova to regulate neuron-specific alternative splicing.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:6350-6355(2000).
RN [8]
RP FUNCTION.
RX PubMed=12808107; DOI=10.1128/mcb.23.13.4687-4700.2003;
RA Dredge B.K., Darnell R.B.;
RT "Nova regulates GABA(A) receptor gamma2 alternative splicing via a distal
RT downstream UCAU-rich intronic splicing enhancer.";
RL Mol. Cell. Biol. 23:4687-4700(2003).
RN [9]
RP FUNCTION.
RX PubMed=14615540; DOI=10.1126/science.1090095;
RA Ule J., Jensen K.B., Ruggiu M., Mele A., Ule A., Darnell R.B.;
RT "CLIP identifies Nova-regulated RNA networks in the brain.";
RL Science 302:1212-1215(2003).
RN [10]
RP FUNCTION, AND PHOSPHORYLATION AT SER-154.
RX PubMed=15933722; DOI=10.1038/sj.emboj.7600630;
RA Dredge B.K., Stefani G., Engelhard C.C., Darnell R.B.;
RT "Nova autoregulation reveals dual functions in neuronal splicing.";
RL EMBO J. 24:1608-1620(2005).
RN [11]
RP FUNCTION.
RX PubMed=17065982; DOI=10.1038/nature05304;
RA Ule J., Stefani G., Mele A., Ruggiu M., Wang X., Taneri B., Gaasterland T.,
RA Blencowe B.J., Darnell R.B.;
RT "An RNA map predicting Nova-dependent splicing regulation.";
RL Nature 444:580-586(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [13]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=30638744; DOI=10.1016/j.neuron.2018.12.019;
RA Saito Y., Yuan Y., Zucker-Scharff I., Fak J.J., Jereb S., Tajima Y.,
RA Licatalosi D.D., Darnell R.B.;
RT "Differential NOVA2-Mediated Splicing in Excitatory and Inhibitory Neurons
RT Regulates Cortical Development and Cerebellar Function.";
RL Neuron 101:707-720.e5(2019).
CC -!- FUNCTION: Functions to regulate alternative splicing in neurons by
CC binding pre-mRNA in a sequence-specific manner to activate exon
CC inclusion or exclusion (PubMed:8558240, PubMed:15933722,
CC PubMed:17065982, PubMed:14615540). It binds specifically to the
CC sequences 5'-YCAY-3' and regulates splicing in only a subset of
CC regulated exons (PubMed:9154818, PubMed:8558240, PubMed:14615540).
CC Binding to an exonic 5'-YCAY-3' cluster changes the protein complexes
CC assembled on pre-mRNA, blocking U1 snRNP binding and exon inclusion,
CC whereas binding to an intronic 5'-YCAY-3' cluster enhances spliceosome
CC assembly and exon inclusion (PubMed:10719891). Binding to 5'-YCAY-3'
CC clusters results in a local and asymmetric action to regulate
CC spliceosome assembly and alternative splicing in neurons. Binding to an
CC exonic 5'-YCAY-3' cluster changed the protein complexes assembled on
CC pre-mRNA, blocking U1 snRNP (small nuclear ribonucleoprotein) binding
CC and exon inclusion, whereas binding to an intronic 5'-YCAY-3' cluster
CC enhanced spliceosome assembly and exon inclusion (PubMed:17065982,
CC PubMed:15933722). With NOVA1, they perform unique biological functions
CC in different brain areas and cell types (PubMed:30638744).
CC Autoregulates its own expression by acting as a splicing repressor
CC (PubMed:15933722). Acts to activate the inclusion of exon E3A in the
CC glycine receptor alpha-2 chain and of exon E9 in gamma-aminobutyric-
CC acid receptor gamma-2 subunit via a distal downstream UCAU-rich
CC intronic splicing enhancer (PubMed:12808107). Acts to regulate a novel
CC glycine receptor alpha-2 chain splice variant (alpha-2N) in developing
CC spinal cord (PubMed:17065982). {ECO:0000269|PubMed:10719891,
CC ECO:0000269|PubMed:12808107, ECO:0000269|PubMed:14615540,
CC ECO:0000269|PubMed:15933722, ECO:0000269|PubMed:17065982,
CC ECO:0000269|PubMed:30638744, ECO:0000269|PubMed:8558240,
CC ECO:0000269|PubMed:9154818}.
CC -!- SUBUNIT: Interacts with PTBP2; the interaction is direct.
CC {ECO:0000269|PubMed:10829067}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8558240}.
CC -!- TISSUE SPECIFICITY: Expressed in neurons of the cortex, sub-cortex,
CC cerebellum and brainstem (at protein level)(PubMed:10829067). Expressed
CC in motor neurons, but not in glia (PubMed:10829067).
CC {ECO:0000269|PubMed:10829067, ECO:0000269|PubMed:8558240}.
CC -!- DOMAIN: The KH domain consists of approximately 70 amino acids and
CC includes a conserved hydrophobic core, an invariant Gly-X-X-Gly motif,
CC and an additional variable segment. The third KH domain (KH3) binds a
CC hairpin RNA loop containing the 5'-UCAY-3' motif on targeted molecules.
CC RNA binding by KH3 requires residues C-terminal to the KH domain.
CC {ECO:0000250|UniProtKB:P51513}.
CC -!- DISEASE: Note=Defects in Nova1 leads to neuronal death in spinal and
CC brainstem neurons. {ECO:0000269|PubMed:10719891}.
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DR EMBL; AC108802; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC156636; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF232828; AAF35907.1; -; mRNA.
DR EMBL; AK047565; BAC33088.1; -; mRNA.
DR CCDS; CCDS49058.1; -.
DR RefSeq; NP_067336.1; NM_021361.1.
DR AlphaFoldDB; Q9JKN6; -.
DR SMR; Q9JKN6; -.
DR BioGRID; 576757; 3.
DR IntAct; Q9JKN6; 1.
DR STRING; 10090.ENSMUSP00000021438; -.
DR iPTMnet; Q9JKN6; -.
DR PhosphoSitePlus; Q9JKN6; -.
DR MaxQB; Q9JKN6; -.
DR PaxDb; Q9JKN6; -.
DR PeptideAtlas; Q9JKN6; -.
DR PRIDE; Q9JKN6; -.
DR ProteomicsDB; 252847; -.
DR Antibodypedia; 133; 261 antibodies from 34 providers.
DR Ensembl; ENSMUST00000021438; ENSMUSP00000021438; ENSMUSG00000021047.
DR GeneID; 664883; -.
DR KEGG; mmu:664883; -.
DR UCSC; uc007nmd.2; mouse.
DR CTD; 4857; -.
DR MGI; MGI:104297; Nova1.
DR VEuPathDB; HostDB:ENSMUSG00000021047; -.
DR eggNOG; KOG2191; Eukaryota.
DR GeneTree; ENSGT00940000155573; -.
DR HOGENOM; CLU_022670_1_1_1; -.
DR InParanoid; Q9JKN6; -.
DR OMA; MTTLANY; -.
DR OrthoDB; 1167935at2759; -.
DR PhylomeDB; Q9JKN6; -.
DR TreeFam; TF316981; -.
DR BioGRID-ORCS; 664883; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Nova1; mouse.
DR PRO; PR:Q9JKN6; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q9JKN6; protein.
DR Bgee; ENSMUSG00000021047; Expressed in lumbar subsegment of spinal cord and 188 other tissues.
DR ExpressionAtlas; Q9JKN6; baseline and differential.
DR Genevisible; Q9JKN6; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:MGI.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:1990825; F:sequence-specific mRNA binding; IDA:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IDA:MGI.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IGI:YuBioLab.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0050684; P:regulation of mRNA processing; ISO:MGI.
DR GO; GO:0051252; P:regulation of RNA metabolic process; IGI:MGI.
DR Gene3D; 3.30.1370.10; -; 3.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR033086; NOVA1.
DR PANTHER; PTHR10288:SF229; PTHR10288:SF229; 1.
DR Pfam; PF00013; KH_1; 3.
DR SMART; SM00322; KH; 3.
DR SUPFAM; SSF54791; SSF54791; 3.
DR PROSITE; PS50084; KH_TYPE_1; 3.
PE 1: Evidence at protein level;
KW mRNA processing; mRNA splicing; Neurogenesis; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding.
FT CHAIN 1..507
FT /note="RNA-binding protein Nova-1"
FT /id="PRO_0000050117"
FT DOMAIN 49..116
FT /note="KH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 171..237
FT /note="KH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 421..488
FT /note="KH 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 139..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 419..503
FT /note="Required for RNA binding"
FT /evidence="ECO:0000250|UniProtKB:P51513"
FT MOTIF 27..43
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 20..34
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15933722"
FT MUTAGEN 444
FT /note="L->N: Strongly decreases RNA-binding."
FT /evidence="ECO:0000269|PubMed:8558240"
SQ SEQUENCE 507 AA; 51756 MW; EB68F2D777BF8135 CRC64;
MMAAAPIQQN GTHTGVPIDL DPPDSRKRPL EAPPEAGSTK RTNTGEDGQY FLKVLIPSYA
AGSIIGKGGQ TIVQLQKETG ATIKLSKSKD FYPGTTERVC LIQGTIEALN AVHGFIAEKI
REMPQNVAKT EPVSILQPQT TVNPDRIKQT LPSSPTTTKS SPSDPMTTSR ANQVKIIVPN
STAGLIIGKG GATVKAIMEQ SGAWVQLSQK PDGINLQERV VTVSGEPEQN RKAVELIIQK
IQEDPQSGSC LNISYANVTG PVANSNPTGS PYANTAEVLP TAAAAAGLLG HANLAGVAAF
PAVLSGFTGN DLVAITSALN TLASYGYNLN TLGLGLSQAA ATGALAAAAA SANPAAAAAN
LLATYASEAS ASGSTAGGTA GTFALGSLAA ATAATNGYFG AASPLAASAI LGTEKSTDGS
KDVVEIAVPE NLVGAILGKG GKTLVEYQEL TGARIQISKK GEFVPGTRNR KVTITGTPAA
TQAAQYLITQ RITYEQGVRA ANPQKVG
